Tumor necrosis factor alpha (TNF-α) is a cytokine produced by numerous cell types, including monocytes and macrophages, that was originally identified based on its ability to induce the necrosis of certain mouse tumors. TNF-α has been implicated in the pathophysiology of a variety of other human diseases and disorders, including shock, sepsis, infections, autoimmune diseases, rheumatoid arthritis, Crohn's disease, transplant rejection, and graft-versus-host disease.
Because of the harmful role of TNF-α in a variety of human diseases and disorders, therapeutic strategies have been designed to inhibit or counteract TNF-α activity. Antibodies that bind to, and neutralize, TNF-α have been sought as a means to inhibit TNF-α activity. In particular, biological therapies have been applied to the treatment of inflammatory disorders such as Crohn's disease and autoimmune disorders such as rheumatoid arthritis. Examples of TNF-α inhibitors include REMICADE™ (infliximab), ENBREL™ (etanercept), HUMIRA™ (adalimumab), and CIMZIA® (certolizumab pegol). While such biological therapies have demonstrated success in the treatment of Crohn's disease and rheumatoid arthritis, not all subjects treated respond, or respond well, to such therapy. Moreover, the administration of TNF-α inhibitors can induce an immune response to the drug and lead to the production of autoantibodies such as human anti-chimeric antibodies (HACA), human anti-humanized antibodies (HAHA), and human anti-mouse antibodies (HAMA). Such HACA, HAHA, or HAMA immune responses can be associated with hypersensitive reactions and dramatic changes in pharmacokinetics and biodistribution of the immunotherapeutic TNF-α inhibitor that preclude further treatment with the drug. Thus, there is a need in the art for selecting a therapeutic regimen with TNF-α inhibitors that is both efficacious and reduces the risk of autoantibody formation to the drug, thereby improving patient outcomes. The present invention satisfies this need and provides related advantages as well.